{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:44:10Z","timestamp":1789753450931,"version":"4.0.1"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Carnitine is a vitamin-like substance that regulates lipid metabolism and energy production. Carnitine homeostasis is mainly regulated by dietary intake and biosynthesis in the organs, including the skeletal muscle and the liver. Therefore, liver cirrhotic patients with reduced food intake, malnutrition, biosynthetic disorder, and poor storage capacity of carnitine in the skeletal muscle and liver are more likely to experience carnitine deficiency. In particular, liver cirrhotic patients with sarcopenia are at a high risk for developing carnitine deficiency. Carnitine deficiency impairs the important metabolic processes of the liver, such as gluconeogenesis, fatty acid metabolism, albumin biosynthesis, and ammonia detoxification by the urea cycle, and causes hypoalbuminemia and hyperammonemia. Carnitine deficiency should be suspected in liver cirrhotic patients with severe malaise, hepatic encephalopathy, sarcopenia, muscle cramps, and so on. Importantly, the blood carnitine level does not always decrease in patients with liver cirrhosis, and it sometimes exceeds the normal level. Therefore, patients with liver cirrhosis should be treated as if they are in a state of relative carnitine deficiency at the liver, skeletal muscle, and mitochondrial levels, even if the blood carnitine level is not decreased. Recent clinical trials have revealed the effectiveness of carnitine supplementation for the complications of liver cirrhosis, such as hepatic encephalopathy, sarcopenia, and muscle cramps. In conclusion, carnitine deficiency is not always rare in liver cirrhosis, and it requires constant attention in the daily medical care of this disease. Carnitine supplementation might be an important strategy for improving the quality of life of patients with liver cirrhosis.<\/jats:p>","DOI":"10.3390\/nu12071915","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T05:28:56Z","timestamp":1593408536000},"page":"1915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Usefulness of Carnitine Supplementation for the Complications of Liver Cirrhosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7797-9534","authenticated-orcid":false,"given":"Tatsunori","family":"Hanai","sequence":"first","affiliation":[{"name":"Department of Gastroenterology\/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Shiraki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Suetugu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Takai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1151-2058","authenticated-orcid":false,"given":"Masahito","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0091-7435(86)90005-8","article-title":"Carnitine: An overview of its role in preventive medicine","volume":"15","author":"Kendler","year":"1986","journal-title":"Prev. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000012825","article-title":"L-Carnitine, a \u2018Vitamin-like substance\u2019 for functional food. Proceedings of the Symposium on L-carnitine, April 28 to May 1, 2000, Zermatt, Switzerland","volume":"44","author":"Walter","year":"2000","journal-title":"Ann. Nutr. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"165720","DOI":"10.1016\/j.bbadis.2020.165720","article-title":"Metabolic interactions between peroxisomes and mitochondria with a special focus on acylcarnitine metabolism","volume":"1866","author":"Houten","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1006\/abbi.1993.1216","article-title":"The carnitine acyltransferases and their role in modulating acyl-CoA pools","volume":"302","author":"Ramsay","year":"1993","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s40620-013-0002-7","article-title":"Effect of L-carnitine therapy on patients in maintenance hemodialysis: A systematic review and meta-analysis","volume":"27","author":"Yang","year":"2014","journal-title":"J. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.mam.2004.06.006","article-title":"Carnitine: A nutritional, biosynthetic, and functional perspective","volume":"25","author":"Steiber","year":"2004","journal-title":"Mol. Asp. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.addr.2009.04.024","article-title":"Carnitine, mitochondrial function and therapy","volume":"61","author":"Zammit","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0065-3101(24)00155-5","article-title":"New genetic defects in mitochondrial fatty acid oxidation and carnitine deficiency","volume":"34","author":"Stanley","year":"1987","journal-title":"Adv. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/07315724.1986.10720124","article-title":"Carnitine as an essential nutrient","volume":"5","author":"Borum","year":"1986","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/hepr.12750","article-title":"Carnitine dynamics and their effects on hyperammonemia in cirrhotic Japanese patients","volume":"47","author":"Shiraki","year":"2017","journal-title":"Hepatol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/0024-3205(96)00343-8","article-title":"Carnitine metabolism in chronic liver disease","volume":"59","author":"Krahenbuhl","year":"1996","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1212\/WNL.31.7.819","article-title":"Primary systemic carnitine deficiency. II. Renal handling of carnitine","volume":"31","author":"Engel","year":"1981","journal-title":"Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1177\/0883073895010002S03","article-title":"Primary and secondary carnitine deficiency syndromes","volume":"10","author":"Pons","year":"1995","journal-title":"J. Child Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1750-1172-7-68","article-title":"Systemic primary carnitine deficiency: An overview of clinical manifestations, diagnosis, and management","volume":"7","author":"Magoulas","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1172\/JCI108824","article-title":"Deficiency of carnitine in cachectic cirrhotic patients","volume":"60","author":"Rudman","year":"1977","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/hep.1840030413","article-title":"Elevated plasma carnitine in hepatic cirrhosis","volume":"3","author":"Fuller","year":"1983","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Miyaaki, H., Kobayashi, H., Miuma, S., Fukusima, M., Sasaki, R., Haraguchi, M., and Nakao, K. (2020). Blood carnitine profiling on tandem mass spectrometry in liver cirrhotic patients. BMC Gastroenterol., 20.","DOI":"10.1186\/s12876-020-01190-6"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.bbrc.2003.07.016","article-title":"Branched-Chain amino acids as a protein- and energy-source in liver cirrhosis","volume":"313","author":"Moriwaki","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.nut.2014.07.005","article-title":"Sarcopenia impairs prognosis of patients with liver cirrhosis","volume":"31","author":"Hanai","year":"2015","journal-title":"Nutrition"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"863","DOI":"10.14740\/jocmr2734w","article-title":"Effect of L-carnitine in patients with liver cirrhosis on energy metabolism using indirect calorimetry: A pilot study","volume":"8","author":"Sakai","year":"2016","journal-title":"J. Clin. Med. Res."},{"key":"ref_21","unstructured":"Shils, M.E., Olson, J.A., Shike, M., and Ross, A.C. (1999). Carnitine. Modern Nutrition in Health and Disease, Lippincott Williams and Wilkins. [9th ed.]."},{"key":"ref_22","first-page":"1","article-title":"The science behind a conditionally essential nutrient. Proceedings of a conference. March 25\u201326, 2004. Bethesda, Maryland, USA","volume":"1033","author":"Daniel","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nm.3145","article-title":"Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis","volume":"19","author":"Koeth","year":"2013","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1172\/JCI94601","article-title":"L-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans","volume":"129","author":"Koeth","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF03168229","article-title":"Carnitine worsens both injury and recovery of contractile function after transient ischemia in perfused rat heart","volume":"64","author":"Diaz","year":"2008","journal-title":"J. Physiol. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1159\/000073347","article-title":"L-Carnitine in the treatment of mild or moderate hepatic encephalopathy","volume":"21","author":"Malaguarnera","year":"2003","journal-title":"Dig. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7197","DOI":"10.3748\/wjg.v11.i45.7197","article-title":"Effects of L-carnitine in patients with hepatic encephalopathy","volume":"11","author":"Malaguarnera","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1007\/s10620-006-9187-0","article-title":"Effects of L-acetylcarnitine on cirrhotic patients with hepatic coma: Randomized double-blind, placebo-controlled trial","volume":"51","author":"Malaguarnera","year":"2006","journal-title":"Dig. Dis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1007\/s10620-008-0238-6","article-title":"Acetyl-L-carnitine treatment in minimal hepatic encephalopathy","volume":"53","author":"Malaguarnera","year":"2008","journal-title":"Dig. Dis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1097\/MEG.0b013e328309c791","article-title":"Branched chain amino acids supplemented with L-acetylcarnitine versus BCAA treatment in hepatic coma: A randomized and controlled double blind study","volume":"21","author":"Malaguarnera","year":"2009","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"799","DOI":"10.3945\/ajcn.110.007393","article-title":"Oral acetyl-L-carnitine therapy reduces fatigue in overt hepatic encephalopathy: A randomized, double-blind, placebo-controlled study","volume":"93","author":"Malaguarnera","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s11011-011-9260-z","article-title":"Acetyl-L-carnitine improves cognitive functions in severe hepatic encephalopathy: A randomized and controlled clinical trial","volume":"26","author":"Malaguarnera","year":"2011","journal-title":"Metab. Brain Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15761\/JTS.1000220","article-title":"L-Carnitine reduces ammonia levels and alleviates covert encephalopathy: A randomized trial","volume":"4","author":"Nojiri","year":"2018","journal-title":"J. Transl. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1002\/hep4.1207","article-title":"L-Carnitine suppresses loss of skeletal muscle mass in patients with liver cirrhosis","volume":"2","author":"Ohara","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/hep4.1309","article-title":"Levocarnitine use is associated with improvement in sarcopenia in patients with liver cirrhosis","volume":"3","author":"Hiramatsu","year":"2019","journal-title":"Hepatol. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/j.cgh.2014.12.005","article-title":"L-Carnitine reduces muscle cramps in patients with cirrhosis","volume":"13","author":"Nakanishi","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1097\/MEG.0000000000001368","article-title":"Can L-carnitine supplementation and exercise improve muscle complications in patients with liver cirrhosis who receive branched-chain amino acid supplementation?","volume":"31","author":"Hiraoka","year":"2019","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1016\/j.cgh.2015.06.039","article-title":"Covert and overt hepatic encephalopathy: Diagnosis and management","volume":"13","author":"Patidar","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S1665-2681(19)31323-7","article-title":"Oral acetyl-L-carnitine treatment in hepatic encephalopathy: View of evidence-based medicine","volume":"12","author":"Jiang","year":"2013","journal-title":"Ann. Hepatol."},{"key":"ref_40","first-page":"CD011451","article-title":"Acetyl-L-carnitine for patients with hepatic encephalopathy","volume":"1","author":"Gluud","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.cgh.2011.08.028","article-title":"Muscle wasting is associated with mortality in patients with cirrhosis","volume":"10","author":"Prado","year":"2012","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1111\/hepr.12774","article-title":"Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria","volume":"46","author":"Nishikawa","year":"2016","journal-title":"Hepatol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s00535-019-01605-6","article-title":"Sarcopenia in cirrhosis: From pathogenesis to interventions","volume":"54","author":"Ebadi","year":"2019","journal-title":"J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s13539-011-0017-7","article-title":"L-Carnitine and cancer cachexia: Clinical and experimental aspects","volume":"2","author":"Silverio","year":"2011","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1038\/ki.1994.460","article-title":"Selective trophic effect of L-carnitine in type I and IIa skeletal muscle fibers","volume":"46","author":"Giovenali","year":"1994","journal-title":"Kidney Int."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Fielding, R., Riede, L., Lugo, J.P., and Bellamine, A. (2018). L-Carnitine supplementation in recovery after exercise. Nutrients, 10.","DOI":"10.3390\/nu10030349"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1111\/liv.13745","article-title":"Relationship of muscle cramps to quality of life and sleep disturbance in patients with chronic liver diseases: A nationwide study","volume":"38","author":"Iwasa","year":"2018","journal-title":"Liver Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1097\/MEG.0000000000001473","article-title":"Clinical features of liver cirrhosis patients with muscle cramping: A multicenter study","volume":"31","author":"Hiraoka","year":"2019","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hoshida, Y. (2019). Risk factors of hepatocellular carcinoma for precision personalized care. Hepatocellular Carcinoma: Translational Precision Medicine Approaches, Humana Press.","DOI":"10.1007\/978-3-030-21540-8"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00281-012-0336-6","article-title":"Obesity and hepatocellular carcinoma: Targeting obesity-related inflammation for chemoprevention of liver carcinogenesis","volume":"35","author":"Shimizu","year":"2013","journal-title":"Semin. Immunopathol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ishikawa, H., Takaki, A., Tsuzaki, R., Yasunaka, T., Koike, K., Shimomura, Y., Seki, H., Matsushita, H., Miyake, Y., and Ikeda, F. (2014). L-Carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100627"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1136\/gutjnl-2017-315193","article-title":"CPT2 downregulation adapts HCC to lipid-rich environment and promotes carcinogenesis via acylcarnitine accumulation in obesity","volume":"67","author":"Fujiwara","year":"2018","journal-title":"Gut"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Nakagawa, H., Hayata, Y., Kawamura, S., Yamada, T., Fujiwara, N., and Koike, K. (2018). Lipid metabolic reprogramming in hepatocellular carcinoma. Cancers, 10.","DOI":"10.3390\/cancers10110447"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, S., Gao, D., and Jiang, Y. (2019). Function, detection and alteration of acylcarnitine metabolism in hepatocellular carcinoma. Metabolites, 9.","DOI":"10.3390\/metabo9020036"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/7\/1915\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:44:16Z","timestamp":1760175856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/7\/1915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,29]]},"references-count":54,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["nu12071915"],"URL":"https:\/\/doi.org\/10.3390\/nu12071915","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,29]]}}}